CN113035686B - Ion source, FAIMS device and method for improving resolution and sensitivity of FAIMS device - Google Patents

Abstract

The application discloses an ion source, a FAIMS device and a method for improving resolution and sensitivity of the FAIMS device. The ion source comprises a first support body, a second support body and an air flow pipeline, wherein the first support body and the second support body are arranged at intervals to form an ion channel, the first support body is provided with a needle electrode, the second support body is provided with an annular electrode, and the tip end of the needle electrode extends into the annular electrode; the gas flow conduit is directed toward the tip of the needle electrode for introducing helium gas to the needle tip. An annular cavity surrounded by the annular electrode is used for introducing nitrogen. According to the ion source provided by the embodiment of the application, the helium environment is arranged around the tip end of the needle-shaped electrode, more ions are ionized in the helium environment, the ion concentration at the entrance of the migration zone is increased, and the ion signal intensity is increased along with the increase of the ion concentration. The ions with increased ionization are larger than the ions lost by the impact migration polar plate, so that the overall ion signal intensity is enhanced, and the resolution and the sensitivity of the high-field asymmetric waveform ion migration spectrum are improved at the same time.

Description

Ion source, FAIMS device and method for improving its resolution and sensitivity

technical field

The invention relates to the technical field of chemical detection, in particular to an ion source, a FAIMS device and a method for improving its resolution and sensitivity.

Background technique

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a rapid chemical detection technology developed on the basis of ion mobility spectrometry. Its mechanism is to carry gaseous chemical substances into the ion source area through the carrier gas and ionize into charged ions. The ionized ions can be separated due to the difference in ion mobility under high and low electric field conditions, so as to detect different substances.

The carrier gas used in the FAIMS device is generally nitrogen, and the resolution corresponding to FAIMS is also different for different carrier gases. Smaller helium, which increases the amplitude of ion motion, increases resolution. However, this method brings about the weakening of ion signal intensity while improving the resolution.

Contents of the invention

The purpose of the embodiments of the present application is to provide an ion source, a FAIMS device and a method for improving its resolution and sensitivity, so as to solve the problem that the resolution and sensitivity of the FAIMS device in the prior art cannot be balanced, and while improving the resolution, it brings A technical problem with the reduction of ion signal strength.

In order to achieve the above object, the technical scheme adopted by the application is:

An ion source, comprising a first support body, a second support body and an air flow channel, the first support body and the second support body are arranged at intervals to form ion channels, the first support body is provided with needle electrodes, and the second support body is provided with The ring electrode, the tip of the needle electrode extends into the ring electrode; the gas flow pipe points to the tip of the needle electrode, and is used to introduce helium gas to the needle tip.

The annular cavity surrounded by the annular electrode is used to introduce nitrogen gas.

In one embodiment, the inside of the needle-shaped electrode has a through hole extending to the needle tip to form a gas flow channel.

In one embodiment, the diameter of the annular cavity is 3-6 times the diameter of the airflow duct, preferably, the diameter of the airflow duct is 0.5-1 mm, and the diameter of the annular cavity is 3 mm-6 mm.

In one of the embodiments, the needle electrode and the ring electrode are arranged concentrically, and the tip of the needle electrode is located in the middle of the axis of the ring electrode;

The second supporting body is provided with a penetrating installation hole, and the hole wall of the installation hole is surrounded by a metal conductive layer to form an annular electrode, and the second supporting body is provided with an air intake pipe communicating with the annular cavity.

A high-field asymmetric waveform ion mobility spectrometer, comprising a housing with an opening at one end, the accommodation chamber of the housing is provided with a migration plate set, a detection plate set and the above-mentioned ion source, and the ion channel faces the opening;

The ion source, the moving pole plate group and the detection pole plate group are arranged in order from far to near in the direction away from the opening.

In one of the embodiments, the casing includes two insulating plates arranged in parallel and separated by a certain distance, and a side plate arranged between the insulating plates, the side plate partially surrounds the insulating plate and forms an opening in the casing;

The first support body and the second support body of the ion source are arranged oppositely, and are distributed on different insulating plates; the moving plate group includes two moving plates arranged oppositely, and the two moving plates are distributed on different insulating plates; The pole plate group includes two opposite detection pole plates, and the two detection pole plates are distributed on different insulating plates.

In one of the embodiments, the first support body and the corresponding insulation board are integrated, and the second support body and the corresponding insulation board are integrated.

In one embodiment, the distance between the two moving plates is 0.2mm˜1mm, and/or the distance between the two detecting plates is 0.2mm˜1mm.

A method for improving the resolution and sensitivity of high-field asymmetric waveform ion mobility spectrometry, comprising the steps of:

Using the above-mentioned high-field asymmetric waveform ion mobility spectrometry, helium gas is passed into the gas flow pipeline, and nitrogen gas is passed into the ring-shaped cavity of the ring electrode; wherein, the flow rate of helium gas is 10-40% of the flow rate of nitrogen gas .

In one embodiment, the flow rate of helium is 0.25-1 L/min, and the flow rate of nitrogen is 1.5-2.25 L/min.

The ion source provided by the embodiment of the present application, when it is used for high-field asymmetric waveform ion mobility spectrometry, since the needle-shaped electrode has a gas flow channel, helium enters from the gas flow channel, so that the surrounding of the tip of the needle-shaped electrode is a helium environment , and helium is easier to ionize than nitrogen. Therefore, with the addition of helium, the discharge current tends to increase, indicating that more ions are ionized in the environment of helium, and the ion concentration at the entrance of the migration zone increases. Therefore, the ion signal intensity increases with the increase of ion concentration. Since helium is a relatively light gas, after mixing helium in nitrogen, the ions are more likely to hit the migration plate in the migration area and be lost, but because the ionized increased ions are greater than the ions lost by hitting the migration plate, the overall The ion signal intensity of the ion is enhanced, which improves the resolution and sensitivity of the high-field asymmetric waveform ion mobility spectrometry at the same time.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the accompanying drawings that need to be used in the descriptions of the embodiments or the prior art will be briefly introduced below. Obviously, the accompanying drawings in the following description are only for the present application For some embodiments, those of ordinary skill in the art can also obtain other drawings based on these drawings without paying creative efforts.

Fig. 1 is the structural representation of the ion source provided by the embodiment of the present application;

FIG. 2 is a schematic structural diagram of an ion source provided by another embodiment of the present application;

Figure 3 is a schematic diagram of the explosion structure of the high-field asymmetric waveform ion mobility spectrum provided by the embodiment of the present application;

Fig. 4 is a schematic structural diagram of a high-field asymmetric waveform ion mobility spectrum provided by another embodiment of the present application;

Fig. 5 is a schematic diagram of the explosive structure of the high-field asymmetric waveform ion mobility spectrum in Fig. 4;

Figures 6a-6d are the effects of adding helium on the FAIMS spectra at different nitrogen flow rates;

Figures 7a-7d show the effects of adding helium on the compensation voltage at different nitrogen flow rates;

Figures 8a-8d show the effects of adding helium on ion signal intensity at different nitrogen flow rates;

Fig. 9a-9c is the analysis of increasing the influence of helium on the ion signal intensity, wherein (9a) is the discharge current, (9b) is the initial discharge voltage, and (9c) is the current (signal) value;

Figures 10a-10b are FAIMS spectra at different gas flow rates, wherein (10a) is pure nitrogen, and (10b) is nitrogen+helium;

Fig. 11 is the FAIMS spectrum comparison of helium and nitrogen under the same mixed gas flow rate;

Figure 12 is the ion intensity and resolution of adding different gases;

Figures 13a-13d are the effects of adding He on the FAIMS spectrum under different radio frequency conditions;

Fig. 14a-14b is the resolution under different radio frequency voltages; Wherein (14a) is the resolution of peak 1, (14b) is the double-peak resolution;

Figures 15a-15c show the effect of helium on ion signal intensity under different radio frequency conditions, where (15a) is peak 1, (15b) is peak 2, and (15c) is peak 3.

Explanation of reference signs:

10. Ion source; 110. First support body; 120. Second support body; 130. Airflow duct; 111. Needle electrode; 121. Ring electrode; 122. Installation hole; 20. Migration plate group; 30. Detecting plate group; 40. shell; 210. moving plate; 310. detecting plate; 510. opening; 410. insulating plate; 420. side plate; 411. upper insulating plate; 412. lower insulating plate.

Detailed ways

In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application clearer, the present application will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present application, not to limit the present application.

It should be noted that when an element is referred to as being “fixed” or “disposed on” another element, it may be directly on the other element or be indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.

It is to be understood that the terms "length", "width", "top", "bottom", "front", "rear", "left", "right", "vertical", "horizontal", "top" , "bottom", "inner", "outer" and other indicated orientations or positional relationships are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the application and simplifying the description, rather than indicating or implying No device or element must have a particular orientation, be constructed, and operate in a particular orientation, and thus should not be construed as limiting the application.

In addition, the terms "first" and "second" are used for descriptive purposes only, and cannot be interpreted as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features. Thus, a feature defined as "first" and "second" may explicitly or implicitly include one or more of these features. In the description of the present application, "plurality" means two or more, unless otherwise specifically defined.

The applicant noticed that the carrier gas used in the existing FAIMS device is nitrogen, and helium with lighter mass and smaller volume was added to it, which brought about the problem of weakening ion signal intensity while improving the resolution. After that, the FAIMS device was studied, and it was found that although helium doping can improve the resolution, due to the small mass and low molecular weight of helium, the movement amplitude of the ions increases, and the number of ions that collide with the polar plate and annihilates increases. , In addition, the increased diffusion movement also causes ion loss and release. Therefore, while the resolution is improved, the ion signal intensity is weakened.

Based on the above problems discovered by the applicant, the applicant improved the structure of the ion source, and the following further describes the embodiments of the present application.

In order to better understand the present application, the following describes the embodiment of the present application with reference to FIG. 1 to FIG. 5 .

1-2, the embodiment of the present application provides an ion source 10, including a first support body 110, a second support body 120 and a gas flow channel 130, the first support body 110 and the second support body 120 are arranged at intervals to form ion channels , the first support body 110 is provided with a needle-shaped electrode 111, the second support body 120 is provided with a ring-shaped electrode 121, and the tip of the needle-shaped electrode 111 extends into the ring-shaped electrode 121; the airflow duct 130 points to the tip of the needle-shaped electrode 111, Used to introduce helium gas to the needle tip.

It can be understood that the ion source 10 may include a housing with at least one opening, and the first support body 110 and the second support body 120 may be two opposite walls of the housing. The opening is an outflow hole for ions generated by the ion source 10 . When other devices are used, it is only necessary to direct the opening toward the ion target area. For example, in high-field asymmetric waveform ion mobility spectrometry, the opening faces the direction where the moving plate set 20 and the detecting plate set 30 are located.

Certainly, the ion source 10 itself may not be provided with a casing. When it is applied to other equipment, the ion source 10 is arranged in the housing 40 of other equipment, and the first support body 110, the second support body 120 and the housing 40 are surrounded to form a channel for ion flow, the same as in high field In the asymmetric waveform ion mobility spectrometer, the position of the ion source 10 can be reasonably arranged so that the ion channel of the ion flow faces the direction where the migration plate set 20 and the detection plate set 30 are located.

The annular cavity surrounded by the annular electrode 121 is used for introducing nitrogen gas. The first supporting body 110 and the second supporting body 120 are arranged opposite to each other, and they are spaced apart from each other by a certain distance, such as being arranged in parallel or at a certain angle. The space between the first support 110 and the second support 120 is an ion channel, and ions generated by ionization of nitrogen and helium can flow along the space between the first support 110 and the second support 120 .

The first support body 110 and the second support body 120 are used to fix the needle electrode 111 and the ring electrode 121 respectively. The shape and size of the first support body 110 and the second support body 120 have no special requirements, and of course relatively thin plates may also be used to facilitate the installation of corresponding electrodes. The first support body 110 and the second support body 120 can be insulating materials, such as PVC and the like.

The ring electrode 121 can be embedded in the second support body 120 , for example, a through ring cavity is opened in the second support body 120 , and the cavity wall is surrounded by electrode material to form the ring electrode 121 . The nitrogen source can communicate with the annular cavity to introduce nitrogen. The annular electrode 121 can also be extended outside the second support body 120, such as the second support body 120 is provided with a hollow cylinder protruding from the surface, the hollow cylinder runs through the second support body 120, and is away from the second support body 120. The end is surrounded by electrode material to form a ring-shaped electrode 121 . The nitrogen source can be communicated with the hollow cylinder to introduce nitrogen. A source of nitrogen can communicate with the hollow cylinder through a conduit.

Referring to FIGS. 1-2 , the tip of the needle electrode 111 protrudes into the ring electrode 121 . One end of the gas flow pipe 130 is connected with an external helium gas source, and the other end points to the tip of the needle-shaped electrode 111 , so that the helium gas is introduced to the vicinity of the tip of the needle-shaped electrode 111 . The airflow pipe 130 can be metal pipes, such as steel pipes, copper pipes, etc., or non-metal pipes, such as plastic pipes, rubber pipes, etc. It is preferably a non-metallic tube to reduce interference with the discharge between the needle electrode 111 and the ring electrode 121 . Helium gas is introduced into the vicinity of the tip of the needle-shaped electrode 111, so that the surrounding of the tip of the needle-shaped electrode 111 is a helium environment, and helium is more easily ionized than nitrogen. Therefore, with the addition of helium, the discharge current tends to increase . It shows that more ions are ionized in the environment of helium, and the ion concentration at the entrance of the migration region increases, so the ion signal intensity increases with the increase of ion concentration. Because helium is a relatively light gas, after mixing helium in nitrogen, ions are more likely to hit the migration plate 210 in the migration region and be lost, but because the ions increased by ionization are greater than the ions lost by hitting the migration plate 210, Therefore, the overall ion signal intensity is enhanced, which simultaneously improves the resolution and sensitivity of the high-field asymmetric waveform ion mobility spectrum.

Referring to FIG. 1 , in one embodiment, the needle electrode 111 has a through hole extending to the needle tip to form a gas flow channel 130 .

In this embodiment, the needle-shaped electrode 111 is a hollow structure that penetrates to the needle tip, and the gas flow channel 130 is integrated in the middle of the needle-shaped electrode 111 . The needle electrode 111 can be a medical disposable sterile injection needle. The end away from the needle tip is connected with helium gas, and the helium gas is introduced into the needle tip. The helium gas flows directly from the needle tip, and there is less resistance to overcome the nitrogen gas, and the needle tip can be surrounded at a lower flow rate to provide a helium atmosphere. Helium flows out from the end face of the needle tip, so the helium concentration distribution around the needle tip is relatively uniform. In addition, the airflow duct 130 is integrated in the middle of the needle electrode 111, the whole device has a high degree of integration, a simplified structure and a reduced volume.

Preferably, the gas flow channel 130 is arranged at the axis of the needle electrode 111, and the helium concentration distribution around the needle tip is more uniform.

Referring to Fig. 1, in one of the embodiments, the diameter of the annular cavity is 3 to 6 times the diameter of the airflow duct 130, preferably, the diameter of the airflow duct 130 is 0.5 to 1 mm, and the diameter of the annular cavity is 3 mm ~6mm.

Referring to FIG. 1 , in one embodiment, the needle electrode 111 and the ring electrode 121 are arranged concentrically, and the tip of the needle electrode 111 is located in the middle of the axis of the ring electrode 121; the second support body 120 is provided with a through mounting hole The hole wall of the installation hole is surrounded by a metal conductive layer to form an annular electrode 121, and the second support body 120 is provided with an air intake pipe installation hole communicating with the annular cavity.

The wall of the second support body 120 is provided with a through installation hole, and the hole wall of the installation hole is surrounded by a metal conductive layer to form a ring electrode 121. The ring electrode 121 is integrated on the wall body of the second support body 120, reducing the ring size. The total thickness of the shape electrode 121 and the second support body 120 is reduced, and the structure is more simplified.

A high-field asymmetric waveform ion mobility spectrometer, referring to FIGS. 3 to 5 , includes a housing 40 with an opening 510 at one end, and the accommodation chamber of the housing 40 is provided with a migration plate set 20, a detection plate set 30 and the above-mentioned ion mobility spectrometer. The source 10 and the ion channel are facing the opening 510 ; the ion source 10 , the transfer plate set 20 and the detection plate set 30 are arranged in sequence from far to near in the direction away from the opening 510 .

The area of the ion source 10 in the shell 40 is the ionization area, the area of the transfer plate set 20 in the shell 40 is the transfer area, and the area of the detection plate set 30 in the shell 40 is the detection area.

The ion source 10 includes a needle electrode 111 and a ring electrode 121. After the sample gas is ionized into charged ions in the ionization region, the carrier gas carries it into the migration region. The moving plate set 20 includes two moving plates 210 opposite to each other. The two moving plates 210 can be supplied with a high-voltage asymmetric wave with a frequency of 1 MHz and a duty ratio of 30% and a compensation voltage with a scanning range of -13V to 13V. After the charged ions that do not meet the experimental requirements are filtered out in the migration area, the rest of the ions reach the detection area. The detection area includes two opposite detection pole plates 310, and a voltage of 9V is added to the two detection pole plates 310, so that the ions can The deflection reaches the detection substrate and is detected by the subsequent weak current detector, and the detected weak signal value is uploaded to the microprocessor controller.

For the above-mentioned high-field asymmetric waveform ion mobility spectrum, due to the use of the above-mentioned ion source 10, the ionization increased ions are greater than the ions lost by hitting the migration plate 210, so the overall ion signal strength is enhanced, thus improving the high-field asymmetric waveform at the same time. Resolution and sensitivity of ion mobility spectrometry.

In one of the embodiments, referring to FIGS. 3 to 5 , the housing 40 includes two insulating plates 410 arranged in parallel and spaced at a certain distance, and a side plate 420 disposed between the insulating plates 410 , the side plate 420 partially surrounds the insulating plate 410 , an opening 510 is formed in the casing 40; the first support body 110 and the second support body 120 of the ion source 10 are arranged oppositely, and are distributed on different insulating plates 410; the moving plate group 20 includes two moving moving plates arranged oppositely 210 , the two moving plates 210 are distributed on different insulating plates 410 ; the detecting plate group 30 includes two oppositely disposed detecting plates 310 , and the two detecting plates 310 are distributed on different insulating plates 410 .

The two transfer plates 210 may be two opposing copper-clad electrodes, and each copper-clad electrode is correspondingly arranged on an insulating plate 410 . Similarly, the two detection pole plates 310 may be two oppositely arranged copper-clad electrodes, and each copper-clad electrode is correspondingly arranged on an insulating plate 410 . The first supporting body 110 is fixed on an insulating board 410 , and the second supporting body 120 is fixed on another insulating board 410 .

In one embodiment, referring to FIGS. 3-5 , the first support body 110 and the corresponding insulating plate 410 are integrally structured, and the second support body 120 and the corresponding insulating plate 410 are integrally structured. In this design, one insulating plate 410 is used as the first supporting body 110, and the other insulating plate 410 is used as the second supporting body. The integration degree of the whole device is higher, and the structure is more streamlined.

In one embodiment, referring to FIGS. 3-5 , the distance between the two moving plates 210 is 0.2 mm˜1 mm, and/or the distance between the two detecting plates 310 is 0.2 mm˜1 mm.

A method for improving the resolution and sensitivity of high-field asymmetric waveform ion mobility spectrometry, comprising the steps of:

Using the above-mentioned high-field asymmetric waveform ion mobility spectrometry, helium gas is passed into the gas flow pipe 130, and nitrogen gas is passed into the annular cavity of the ring electrode 121; wherein, the flow rate of helium gas is 10-10% of the flow rate of nitrogen gas. 40%.

In one embodiment, the flow rate of helium is 0.25-1 L/min, and the flow rate of nitrogen is 1.5-2.25 L/min.

The technical solution of the present application will be introduced below in combination with specific embodiments.

1. Experimental device

The FAIMS experimental platform consists of a sampling module (helium unit and sampling unit), a FAIMS device, a weak current detector, a power supply module, a microprocessor controller and a spectrum display module. The carrier gas used in the experiment is high-purity nitrogen and high-purity helium (produced by Guangxi Ruida Chemical Technology Co., Ltd., 99.999%), and the flowmeter is D08-1F flow display instrument and CS200A digital gas mass flow controller (Beijing Qixing Huachuang Electronics Co., Ltd.), the measurable gas flow range is 0-5L min ^-1 , and the adjustment accuracy is 0.01L min ^-1 ; the experimental sample is untreated volatile organic ethanol (CH3CH2OH, Xilong Chemical Co., Ltd., 99.7%), the experiment was carried out at normal temperature and pressure.

Put the small flask containing the ethanol sample into the sample cell (height 4cm, diameter 3.5cm), the entire sample unit is connected by a gas pipe through a pneumatic interface, and the carrier gas helium is passed through, so that the sample is carried by the helium to the ionization unit of the FAIMS device. in the district.

2. Design and manufacture of FAIMS device

The structural diagram of the PCB-based FAIMS device is shown in FIG. 1 , and for the convenience of description, two insulating plates 410 are defined as an upper insulating plate 411 and a lower insulating plate 412 . The upper insulating plate 411 and the lower insulating plate 412 are manufactured by PCB technology, and the insulating plates 410 are sealed by PCB brazing process. This device adds a helium ventilation device on the FAIMS system board based on the brazing process. The upper insulating plate 411 and the lower insulating plate 412 are 60mm×40mm and 60mm×55mm in size respectively, and the upper insulating plate 411 and the lower insulating plate 412 Place a 0.2mm spacer between them. The upper insulating plate 411 is composed of a hole with a diameter of 1 mm and two copper-clad electrodes, and the lower insulating plate 412 is composed of a hole with a diameter of 3 mm and two copper-clad electrodes. It is used as a transition zone plate and a detection plate 310 .

The needle-ring discharge structure is used as the ion source 10. After the sample gas is ionized into charged ions in the ionization region, the carrier gas carries it into the migration region, where a high-voltage asymmetric wave with a frequency of 1 MHz and a duty ratio of 30% and The scanning range is -13V～13V compensation voltage. After the charged ions that do not meet the experimental requirements are filtered out in the migration area, the rest of the ions reach the detection area, and a voltage of 9V is applied to the deflection substrate in the detection area, so that the ions can be deflected and reach the detection substrate, so that they are detected by the subsequent weak current detector , and upload the detected weak signal value to the microprocessor controller.

3. Hollow needle-ring ion source

In order to improve the resolution and sensitivity of FAIMS, a helium-nitrogen relative ventilation structure is designed, and the ionization region is composed of needle-ring electrodes. The needle electrode 111 is hollow, and helium enters the ionization region from the hollow part of the needle electrode 111. In this way, helium can pass through the hollow needle electrode 111, so that the needle tip is surrounded by helium, which can increase the Discharge current, improve ionization efficiency. The needle-shaped electrode 111 is a medical disposable sterile injection needle with a hollow inner diameter of 0.26mm, an outer diameter of 0.5mm, and a length of 60mm. The fixed structure of the needle is made of PLA polylactic acid material through 3D printing. The large cylinder is composed of small cylinders with a height of 8mm and a bottom diameter of 3mm. A small hole with a diameter of 1mm is designed on the needle fixing structure and the upper insulating plate 411 to pass through the hollow needle. Helium gas is passed through the hollow needle while ensuring that the hollow needle is in the The ring electrode 121 is right in the middle. The 3mm hole of the lower plate is coated with copper as the discharge anode, which is combined with the hollow needle of the upper plate to form an ionization source. During the experiment, nitrogen carries the sample from the 3mm hole of the lower insulating plate 412 into the needle-ring ionization source for ionization. In order to ensure airtightness, a nitrogen sampling device made of copper was designed and manufactured. The device is composed of cylinders with inner and outer diameters of 16mm and 10mm, respectively, and is directly connected to a PTFE tube with an outer diameter of 4mm through a pneumatic joint.

The needle electrode 111 is connected to the negative pole of the negative DC high voltage power supply through a 6MΩ ballast resistor, wherein the ballast resistor is used to limit the discharge circuit current and suppress spark discharge, and the ring electrode 121 is connected to the ground of the negative DC high voltage power supply through a 1kΩ test resistor. Load an oscilloscope and a multimeter at both ends of the test resistor to obtain the discharge waveform and discharge current generated by the needle-ring asymmetrical electrode discharge. The negative DC high voltage power supply (HB-F203-5AC) ranges from 0 to -20kV.

4. Experimental results

4.1 Improve ion signal intensity and resolution

Under the conditions of discharge voltage -2kV, ballast resistance 6M, RF voltage 300V, and sample ethanol, add 0.2L min ^-1 , 0.3L min ^-1 , 0.5L min ^-1 , 1L min ^-1 at different N ₂ flow rates The proportion of He when He is shown in Table 1. As the flow of N ₂ increases, the proportion of He decreases under the same flow rate. When both N ₂ and He are 1L min ^-1 , the proportion of He reaches the maximum, which is 50%. Therefore, the range of He proportion in this experiment is 0-50%, this range takes into account the breakdown characteristics of He, which is the safe range of the experiment.

Table 1 Helium ratio at different nitrogen flow rates

Figure 6(ad) shows the FAIMS spectra of different He ratios added under the conditions of N ₂ flow rate of 1L min ^-1 , 1.5L min ^-1 , 2L min ^-1 , and 2.5L min ^-1 . It can be seen from the figure that increasing the proportion of He under different N ₂ flow rates can improve the separation ability of the FAIMS spectrum and the ion peak intensity has increased. It is generally believed that the offset voltage peak with a large offset is the monomer peak, followed by the dimer peak , the least biased is the polymer peak, where the three peaks are named peak 1, peak 1, and peak 3. Taking Figure 6c as an example, when the N ₂ flow rate is 2 L/min and the He ratio is 9%, the peak 1 ion signal intensity reaches the maximum, which is 33.45 pA. The proportion of He increased to 20%, and the number of ion peaks changed from two to three. Continue to increase the He ratio to 33%, although the signal intensity has a downward trend, it is still 1.56 times larger than that without He, and the separation of the three peaks becomes more and more obvious, indicating that with the increase of the He ratio, the separation of ion species The effect is getting better and the signal strength has improved.

Figure 7(a-d) is the compensation voltage position map corresponding to the FAIMS spectrum. It can be seen from the figure that as the proportion of He increases, the compensation voltage positions of peak 1, peak 2 and peak 3 also change. Taking Figure 7a as an example, as the proportion of He increases, the positions of peaks 1 and 2 shift downward, while the position of peak 3 shifts upward, and the magnitude of the downward shift of peak 1 is greater than that of peak 2, so that the three The distance between the two peaks becomes larger.

Resolution can be expressed in terms of the peak width of a single peak, the separation between different peaks, or the difference in offset voltage between three peaks. The larger the distance between the compensation voltages, the higher the resolution, otherwise the resolution will gradually decrease. Therefore, it can be seen from the figure that under different _N2 flow rates, the resolution increases with the increase of the He ratio.

In order to more intuitively and clearly see the comparison of the compensation voltage difference between peak 1 and peak 2, peak 2 and peak 3, the influence of applying He on the compensation voltage under different _N2 flow rates in Figure 7 is expressed numerically, As shown in Tables 2 and 3 (wherein "-" indicates that peak 3 has not yet appeared). Table 2 shows the compensation voltage difference between peak 1 and peak 2. Under the same _N2 flow rate, as the proportion of He increases, it can be seen that the difference between the compensation voltage increases gradually, and the difference between peak 1 and peak 2 The degree of separation is getting higher and higher; there is no difference between peak 2 and peak 3 in table 3, because peak 3 has not yet appeared under this condition, and with the increase of He ratio, peak 3 appears, and As the distance from peak 2 increases, the resolution between peak 2 and peak 3 increases, so it is verified again that the resolution increases as the proportion of He increases.

Table 2 Compensation voltage comparison between peak 1 and peak 2

Table 3 Compensation voltage comparison between peak 2 and peak 3

其中K_h和K_l分别为高场和低场条件下的离子迁移率，g为迁移板之间的距离，d为给定的单个射频占空比，E_pp为单个射频高压幅值，d_H为高场占空比。The formula for calculating the compensation voltage is as follows:

where K _h and K _l are the ion mobility under high-field and low-field conditions, respectively, g is the distance between the migration plates, d is a given single radio frequency duty cycle, E _pp is a single radio frequency high voltage amplitude, d _H is the high field duty cycle.

Brown's theorem holds that the ion mobility of the mixed carrier gas is related to the ratio of the mixed gas and its nonlinear change far exceeds the ion mobility change under a single gas. From the above formula, the value of the compensation voltage will vary with the ion mobility However, the greater the value of (K _h -K _l ), the greater the value of the compensation voltage. The experimental phenomenon is consistent with the theoretical research.

Fig. 8(ad) shows the ion signal intensities of different He ratios when the N ₂ flow rates are 1L min ^-1 , 1.5L min ^-1 , 2L min ^-1 , and 2.5L min ^-1 respectively. It can be seen from the figure that when the proportion of He is small, peak 3 will not appear. As the proportion of He increases, the ion signal intensities of the three peaks basically show a trend of first increasing and then decreasing, and peak 1 and peak 2 are respectively at 0.2, The peak value reached the maximum at 0.3L min ^-1 He and then decreased.

Figure 9(ac) shows the analysis of increasing the ion signal intensity by increasing the helium flow rate. The experimental conditions are nitrogen flow rate 1.5L min ^-1 , ballast resistance 6MΩ, under negative DC high voltage, the needle-ring electrode produces corona Discharge and glow discharge, and the discharge current in the circuit is an important parameter to characterize the severity of the discharge. Under the discharge voltage of -2KV, observe the discharge current connected to the 1KΩ test resistor as shown in Figure 9a. From the observation in the figure, it can be seen that applying nitrogen gas on the basis of the nitrogen flow rate of 1.5L min ^-1 has no effect on the discharge current. When the same proportion of helium is applied, the discharge current will gradually increase, and the increase in current value may be due to the fact that more sample ions are ionized as helium is added to the ionization region. Figure 9b shows the effect of applying He on the initial discharge voltage. It can be seen from the figure that adding nitrogen on the basis of nitrogen has no effect on the discharge voltage, while increasing helium will reduce the initial discharge voltage. Figure 9c shows the effect of adding different flows of helium on the ion signal intensity on the basis of nitrogen without applying radio frequency voltage under the condition of continuous scanning of the compensation voltage. It can be seen from the figure that with the increase of helium, the ion signal becomes more and more Strong, it can be confirmed that with the increase of helium flow rate, more ions are ionized in the ionization region.

The formula for calculating ion signal intensity is as follows:

式中：n_in为迁移区入口处的离子浓度，Q为载气流量，t_res为离子经过迁移区的时间，D为离子的扩散系数，g_e为迁移区的有效间距，k_B为波尔兹曼常数，q为离子电荷数，g为迁移区基板间距，T为开氏温度，V_H为方波射频电压幅值，d为占空比，f为方波射频电压频率。

In the formula: n _in is the ion concentration at the entrance of the migration zone, Q is the flow rate of the carrier gas, t _res is the time for the ion to pass through the migration zone, D is the diffusion coefficient of the ion, g _e is the effective distance of the migration zone, k _B is the wave Biltzmann's constant, q is the number of ion charges, g is the distance between the substrates in the migration zone, T is the Kelvin temperature, V _H is the amplitude of the square wave radio frequency voltage, d is the duty cycle, and f is the frequency of the square wave radio frequency voltage.

With the addition of He, the discharge current tends to increase, indicating that more ions are ionized in the He environment, and the ion concentration n _in at the entrance of the migration zone increases. From the above formula, the signal intensity H increases with the ion concentration n increase with the increase of _in . Because He is a relatively light gas, after mixing He in _N , ions are more likely to hit the migration plate 210 in the migration region and be lost. The signal intensity increases, and vice versa, it decreases, which explains why the ion signal intensity first increases and then decreases after increasing the proportion of helium. In the flat plate FAIMS in the early stage test of the present invention, nitrogen and helium have been mixed before entering the ionization region. After adding helium, the ionization efficiency of the ion source cannot be improved, but in the migration region due to the improvement of ion mobility The movement amplitude increases, and the diffusion and space charge effects increase the probability of ions hitting the substrate and annihilating them, thereby reducing the signal.

4.2 Flow control experiment

In order to rule out the effect of adding helium on the FAIMS spectrum due to the increase in flow rate, the following control experiment was done: under the condition of N ₂ flow rate of 2L min ^-1 , a group of dopant gas was added at 0.2L min ^-1 , 0.3Lmin ^-1 , 0.5L min ^-1 and 1L min ^-1 of He, another group of control group doped gas with the same flow rate of N ₂ , observe the changes of the FAIMS spectra of the two groups. Figure 10(ab) is the FAIMS spectrum obtained under the conditions of RF voltage 200V, ballast resistance 6M, and discharge voltage -2KV. It can be seen from Figure 10a that gradually increasing N ₂ on the basis of 2L min ^-1 will only affect The signal strength is affected, but it will not affect the value of the compensation voltage, and the peak width of the curve gradually widens, and the resolution decreases; Figure 10b shows that He is gradually increased on the basis of N ₂ being 2L min ^-1 , it can be seen from the figure that with The increase of the He ratio compensates for the voltage shift to the left, the signal intensity first increases and then decreases, and peak 2 gradually appears, and the resolution improves.

Under the condition that the initial N ₂ flow rate was 2L min ^-1 , the same flow of N ₂ and He were added to the mixed gas for comparison, as shown in Figure 11. Observing the graphs of adding 0.3L min ^-1 He and adding 0.3L min ^-1 N ₂ , it is found that the signal intensity, compensation voltage value and number of peaks are different. Under the condition that the total flow rate is 2.3L min ^-1 , the ion peak signal intensity after adding 0.3L min ^-1 helium gas is 197.3pA, which is 2.83 times of the signal intensity 70pA when adding 0.3L min ^-1 nitrogen gas. At the same time, The compensation voltage is also increased from -1.98V to -2.37V, and the same is true for other flow rates, indicating that the experimental phenomenon caused by increasing the proportion of He is not only caused by the increase of flow rate.

Figure ¹² shows ^the _{N 2 ,} ^{He ionic strength and} Resolution comparison chart. It can be seen from the figure that with the increase of N ₂ , the ion signal intensity gradually increases from the original 52.76pA to 85.68pA, and there is only one peak. The increase of the signal intensity is caused by the flow velocity. With the increase of the proportion of He added, the ion signal intensity first increased and then decreased. When 0.3L min ^-1 He was added, the signal intensity reached 197.26pA, which was 2.83 times the signal intensity of 0.3L/min ^-1 N ₂ . And under this condition, a second peak with an amplitude of 15.22pA appeared, and the reason for the appearance of the second peak was due to the improvement of the resolution.

The formula for calculating the resolution of peak 1 is as follows:

Among them, V _H is the amplitude of the square wave RF voltage, K _L is the ion mobility under low electric field conditions, α(E/N) is the ion mobility coefficient, d is the duty cycle, and k _B is the Boltzmann Constant, T is the Kelvin temperature, q is the ion charge, _tres is the time for the ion to pass through the migration region, R is the resolution, CV is the compensation voltage value, and FWHM is the half-peak width.

It can be seen from the above formula that with the increase of _N2 flow rate, the time _tres for ions to pass through the migration region decreases, resulting in a decrease in resolution. Gradually add He under the condition of 2L min ^-1 N ₂ , and the resolution gradually increases. This is because He is a relatively light gas. With the increase of He, the oscillation of ions in the migration region will be accelerated, thereby improving the ion resolution. The control experiment verified that the effect of adding He on the FAIMS spectrum is not due to the increase of the flow rate.

4.3 Different RF Conditions

其中，R₁为双峰的分离度，CV₁与CV₂分别为峰1与峰2的补偿电压值，W₁与W₂分别为峰1与峰2的峰宽。Under the conditions of discharge voltage -2kV, ballast resistance 6MΩ, and N ₂ flow rate 2L min ^-1 , Fig. 13(ad) shows the FAIMS spectra of different He flow rates under the application of 200V, 250V, 300V, and 350V RF, respectively. It can be seen from the figure that under different radio frequency conditions, with the increase of the proportion of He, the ion signal intensity first increases and then decreases, but the overall signal intensity is still greater than that without adding He. Taking Figure 13b as an example, when adding He to 0.2L min ^-1 , that is, when the proportion of helium is 9% (corresponding to Table 1), the signal intensity of peak 1 increases from 26.82pA without He addition to 84.75pA, increasing increased by 3.15 times. Continue to increase He, and the signal intensity gradually decreases. When the He ratio reaches the maximum value of 33% under the N ₂ flow, the ion signal intensity drops to 61.37pA, but it is still 2.29 times greater than that without He. At the same time, the peak 2 in Figure 13b also has the same rule. When no He is added, the ion signal intensity of peak 2 is only 4.02pA. With the addition of He, the ion signal intensity reaches 8.36pA at 0.3L min ^-1 He , and then decreased to 5.9pA, but still larger than 4.02pA. This experimental phenomenon proves that increasing He can increase the sensitivity (signal intensity) of ions. The formula for calculating the resolution between two peaks is as follows:

Among them, R ₁ is the separation degree of the double peaks, CV ₁ and CV ₂ are the compensation voltage values of peak 1 and peak 2 respectively, W ₁ and W ₂ are the peak widths of peak 1 and peak 2 respectively.

Figure 14a shows the resolution value of peak 1 calculated by the formula under different radio frequency conditions. It can be seen from the figure that as the proportion of He increases, the peak width becomes narrower, the compensation voltage becomes larger, and the resolution of the monomer peak increases. , 250V, 300V, and 350V, when 1L min ^-1 He was added, the resolution reached the highest, which was 1.61, 1.90, 1.61, and 2.34 times higher than that without He, respectively. Figure 14b shows the separation between peak 1 and peak 2 calculated by the formula under the conditions of RF voltage 250V, 300V, and 350V. As the proportion of He increases, the separation between the two peaks becomes larger and further improves the resolution. . It can be seen from Figure 14a that when the RF voltage is 200V and the He ratio is 13%, double peaks appear, but because peak 2 is not completely separated from peak 1, it is difficult to calculate the specific degree of separation by the formula, and increasing He leads to the second The appearance of the peak proves from another angle that increasing He can improve the resolution; when the RF voltage is 300V and 350V respectively, as the proportion of He increases, the third peak gradually appears, which also shows that the resolution increases with the addition of He In addition, the greater the RF voltage, the greater the increase in resolution after adding helium. When the radio frequency voltage is 200V, 250V, 300V, and 350V, the resolution of the monomer peak is increased from 2.13 to 3.42, from 2.67 to 5.09, from 3.39 to 6.55, from 5.31 to 12.43, and the increase is 1.61. 1.91, 1.93, 2.34. When the RF voltage is 250V, 300V, and 350V, the double-peak separation degree increases from 1.57 to 2.6, from 2.33 to 4.37, and from 4.17 to 9.51, and the increasing multiples are 1.66, 1.88, and 2.28.

Figure 15(ac) is the signal intensity change diagram of peak 1, peak 2 and peak 3 with the increase of He ratio under different radio frequency conditions. It can be seen from the figure that with the increase of He ratio, the The signal strength has a tendency to increase first and then decrease, but the peak value can reach the maximum under different He ratios. When the RF voltage is 200V, peak 1 and peak 2 reach the maximum when the flow rate of He is 0.3L min ^-1 . Continue to increase He, and the signal intensity decreases, but it is still greater than that without adding He. At this time, peak 3 has not yet appeared. When the RF voltage is 300V, the signal value of peak 1 is the largest at 0.2L min ^-1 He, peak 2 is the highest at 0.3L min ^-1 He, peak 3 appears at 0.5L min ^-1 He, and reaches the Maximum value at RF conditions, followed by decreasing peak value. In a word, under different radio frequency conditions, increasing He can improve sensitivity, and the influence of radio frequency voltage on sensitivity is just opposite to that on resolution. For peak 1, the smaller the amplitude of the RF voltage, the more obvious the effect of adding helium on improving the signal strength. When the RF voltage is 200V, the signal strength can be increased by a maximum of 3.74 times when 0.3L min ^-1 helium is added. When the RF voltage When it is 350V, the signal strength can only be increased by 1.7 times; the change law of the signal strength of peak 2 and peak 3 is also similar, but a higher RF voltage is required or more helium gas needs to be added under the same voltage condition to appear peak 2 and peak 3.

The experimental results of the present invention show that at 1L min ^-1 , 1.5L min ^-1 , 2L min ^-1 and 2.5L min ^-1 N ₂ flow rates, the addition of He increases the value of the compensation voltage, and the number of ion peaks changes from two Changed to three, the offset voltage distance between different ion peaks increases, which indicates the improved resolution of FAIMS. On the other hand, the signal intensity of the ion peak also increased, indicating that the sensitivity of FAIMS also increased. Under the condition of nitrogen flow rate of 2L min ^-1 , the same flow rate of helium and nitrogen was added as the mixed carrier gas, so that the total flow rate was the same and different The experiment of adding helium under RF voltage also proves that adding helium can improve the resolution and sensitivity of FAIMS at the same time.

The above are only preferred embodiments of the application, and are not intended to limit the application. Any modifications, equivalent replacements and improvements made within the spirit and principles of the application should be included in the protection scope of the application. Inside.

Claims (8)

1. The ion source is characterized by comprising a first support body, a second support body and an air flow pipeline, wherein the first support body and the second support body are arranged at intervals to form an ion channel, the first support body is provided with a needle electrode, the second support body is provided with an annular electrode, and the tip end of the needle electrode stretches into the annular electrode; the airflow pipeline points to the tip of the needle-shaped electrode and is used for introducing helium gas to the needle tip; the annular cavity is surrounded by the annular electrode and is used for introducing nitrogen; the needle electrode is internally provided with a through hole penetrating to the needle point to form the air flow pipeline; the needle-shaped electrode and the annular electrode are concentrically arranged, and the tip end of the needle-shaped electrode is positioned in the middle of the axis of the annular electrode; the second support body is provided with a penetrating mounting hole, a metal conducting layer is arranged around the hole wall of the mounting hole to form the annular electrode, and the second support body is provided with an air inlet pipe communicated with the annular cavity.

2. The ion source of claim 1, wherein the annular cavity has a diameter of 3-6 times the diameter of the gas flow conduit, the gas flow conduit has a diameter of 0.5-1 mm, and the annular cavity has a diameter of 3-6 mm.

3. A FAIMS device comprising a housing having an opening at one end, a receiving cavity of the housing provided with a set of transfer plates, a set of detection plates, and the ion source of any one of claims 1-2, an ion channel facing the opening; the ion source, the migration polar plate group and the detection polar plate group are sequentially arranged from far to near in the direction away from the opening.

4. A FAIMS device according to claim 3, wherein the housing comprises two insulating plates arranged in parallel and spaced apart a distance and a side plate disposed between the insulating plates, the side plate partially surrounding the insulating plates, an opening being formed in the housing; the first support body and the second support body of the ion source are arranged opposite to each other and distributed on different insulating plates; the migration polar plate group comprises two migration polar plates which are oppositely arranged, and the two migration polar plates are distributed on different insulating plates; the detection polar plate group comprises two detection polar plates which are oppositely arranged, and the two detection polar plates are distributed on different insulating plates.

5. The FAIMS device of claim 4, wherein the first support is of unitary construction with the corresponding insulator plate and the second support is of unitary construction with the corresponding insulator plate.

6. The FAIMS device of claim 4, wherein the distance between the two displacement plates is between 0.2mm and 1mm and the distance between the two detection plates is between 0.2mm and 1mm.

7. A method of improving resolution and sensitivity of a FAIMS device comprising the steps of: introducing helium into the airflow pipeline and introducing nitrogen into the annular cavity of the annular electrode by adopting the FAIMS device as claimed in any one of claims 4 to 6; wherein the flow rate of the helium gas is 10-40% of the flow rate of the nitrogen gas.

8. The method of claim 7, wherein the helium flow is 0.25-1L/min and the nitrogen flow is 1.5-2.25L/min.

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